Chymase, a chymotrypsin-like serine protease, has been previously validated as an important target for drug development against cardiovascular disease. Chymase is stored as an inactive enzyme in the secretory granules of mast cells and is involved in the angiotensin-converting enzyme (ACE)-independent synthesis of angiotensin II (Ang II). This process occurs immediately after chymase is released into the interstitial tissues following vascular injury. It has been shown that chymase-positive cells accumulate in atherosclerotic lesions in patients and that chymase inhibition prevented the development of atherosclerosis in an animal model. Cardiac dysfunction after myocardial infarction also has been shown to be attenuated by chymase inhibition. Further, cardiac chymase has been shown to participate directly in the pathophysiologic state after myocardial infarction in hamsters. Inhibition of chymase also may be useful for preventing vascular proliferation in grafted vessels and in the repair of organs affected by stroke.